Total Synthesis of Polyenemacrolide Antibiotics and Related Antibiotics

聚大环内酯类抗生素及相关抗生素的全合成

• 批准号: 60470091
• 负责人: KINOSHITA Mitsuhiro
• 金额: $ 3.46万
• 依托单位: Faculty of Science and Technology, Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1987
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-60470091/
• 关键词: Elaiophylin; Amphotericin B; Aglycon; D-Glucose; 2-Deoxy-1-fucose; ビス(ジトチルチオ)スタニル化合物; アムホテリシンBアグリコン; ワーズワース反応; ビス(メチルチオ)トリメチルスタニル化合物; DIBAL環元; Mn【O_2】酸化

1. Total synthesis of elaiophylin: The antibiotic elaiophylin (1) has been first synthesized by a convergent route involving aldol coupling of (5R, 6R, 7R,)-5-0-(2-deoxy-3, 4-bis- 0-(isopropyldimethylsilyl)-<alpha>-L-fucopyranosyl)-6-ethyl-7-0-(diethylisopropylsilyl)-5, 7-dihydroxy- 3- octanone (2) and (7S, 8S, 15S, 16S: 3E, 5E, 11E, 13E)-8,16--bis-((1R)-1-formylethyl)-7,15-dimethyl-1, 9-dioxa- 3,5,11,13-cyclohexadecateteaene-2, 10-dione (3), followed by desylilation. The segments 2 and 3 were enantiospecifically synthesized from appropriate D-glucose derivative and 2-deoxy-L-fucose.2. Synthesis of amphotericin B aglycon: The key segments 1 and 2 corresponding to the C_1-C_<20> and C_<21>-C_<37> portions of amphotericin B aglycon have been synthesized. The synthesis of 1 was accomplished by a convergent route involving coupling between the iodo compound (C_1-C_<12> segment) and the lithium compound generated from bis (dimethylthio) trimethylstannyl compound (C_<13>-C_<19> segment), intramolecular cycl-ic methyl acetalization, and (dimethoxyphosphinyl) methlation of C_<19>-methoxycarbonyl group. Both the C_1-C_<12> and C_<13>-C_<19> segments were stereoselectively synthesized from appropriate D-glucose derivatives. The unsaturated C_<21>-C_<37> segment was synthesized by the two-fold Horner-%emmons olefination with (2E, 4E)-6-( dimethoxyphosphinyl )-2, 4-hexadienoate of the C_<33>-C_<37> aldehydic segment which was enantiospecifically synthesized from appropriate D-glucose derivative.

1.香豆素的全合成：首次通过(5R，6R，7R，)-5-0-(2-脱氧-3，4-双-0-(异丙基二甲基硅基)-lt；α&Gt；-L-fucopyranosyl)-6-ethyl-7-0-(diethylisopropylsilyl)-5，7-二羟基-3-辛酮(2)和(7S，8S，15S，16S：3E，5E，11E，13E)-8，16--bis-((1R)-1-formylethyl)-7，15-dimethyl-1，9-二氧杂-3，5，11，13-环十六烷-2，10-二酮(3))，然后脱氢。第二段和第三段是由适当的D-葡萄糖衍生物和2-脱氧-L岩藻糖对映体专一性合成的。两性霉素B苷元的合成：合成了两性霉素B苷元的C_1-C_&lt；20&gt；和C_&lt；21&gt；-C_&lt；37&gt；部分关键片段1和2。1的合成是通过碘化合物(C_1-C_t；12)与双(二甲硫基)三甲基锡基化合物(C_&lt；13&gt；-C_&lt；19&gt；)生成的锂化合物、分子内环甲缩合和(二甲氧基膦)甲基化C_&lt；19&甲氧基羰基生成的聚合路线完成的。用合适的D-葡萄糖衍生物立体选择性地合成了C_1-C_&lt；12&gt；和C_&lt；13&gt；-C_&lt；19&gt；片段。C_&lt；33&gt；-C_&lt；37&gt；醛链段是由D-葡萄糖衍生物对映体合成的(2E，4E)-6-(二甲氧基膦)-2，4-己二烯酸酯与C_&lt；21&gt；-C_&lt；37&gt；链段经两次Horner-%Emmons烯化反应合成的。

项目成果

Mitsuhiro Kinoshita, Masato Taniguchi, Masahiko Morioka, Hitoshi Takami, and Yasuhiro Mizusawa: "An Enantiospecific Synthesis of the C-1-C-19 Segment of Amphothericin B Aglycon." Bull. Chem. Soc. Jpn.,. 61. (1988)

Mitsuhiro Kinoshita、Masato Taniguchi、Masahiko Morioka、Hitoshi Takami 和 Yasuhiro Mizusawa：“两性霉素 B 苷元 C-1-C-19 片段的对映特异性合成”。

Kazunobu Toshima, Kuniaki Tatsuta, and Mitsuhiro Kinoshita: "Total Synthesis of Elaiophylin (Azalomycin B)." Tetrahedron Letters. 27(39). 4741-4744 (1986)

Kazunobu Toshima、Kuniaki Tatsuta 和 Mitsuhiro Kinoshita：“Elaiophylin（阿扎霉素 B）的全合成”。

K. Toshima;K. Tatsuta;M. Kinoshita: Bull. Chem. Soc. Jpn.61. (1988)

K.丰岛；K.

木下光博: Bull.Chem.Soc.Jpn.60. (1987)

木下光宏：Bull.Chem.Soc.Jpn.60 (1987)。

Mitsuhiro Kinoshita;H. Takami;M. Taniguch;T. Tamai: Bull. Chem. Soc. Jpn.60. 2151-2161 (1987)

木下光宏;H.